tbuckley/cabot-search huggingface dataset:
Clinical Validity of 16α-[<sup>18</sup>F]Fluoro-17β-Estradiol Positron Emission Tomography/Computed Tomography to Assess Estrogen Receptor Status in Newly Diagnosed Metastatic Breast Cancer
Authors: Jasper J.L. van Geel, Jorianne Boers, Sjoerd G. Elias, Andor W.J.M. Glaudemans, Erik F.J. de Vries, Geke A.P. Hospers, Michel van Kruchten, Evelien J.M. Kuip, Agnes Jager, Willemien C. Menke-van der Houven van Oordt, Bert van der Vegt, Elisabeth G.E. de Vries, Carolina P. Schröder
Journal: Journal of Clinical Oncology (2022)

Determining the estrogen receptor (ER) status is essential in metastatic breast cancer (MBC) management. Whole-body ER imaging with 16α-[18F]fluoro-17β-estradiol positron emission tomography ([18F]FES-PET) is increasingly used for this purpose. To establish the clinical validity of the [18F]FES-PET, we studied the diagnostic accuracy of qualitative and quantitative [18F]FES-PET assessment to predict ER expression by immunohistochemistry in a metastasis.In a prospective multicenter trial, 200 patients with newly diagnosed MBC underwent extensive workup including molecular imaging. For this subanalysis, ER expression in the biopsied metastasis was related to qualitative whole-body [18F]FES-PET evaluation and quantitative [18F]FES uptake in the corresponding metastasis. A review and meta-analysis regarding [18F]FES-PET diagnostic performance were performed.Whole-body [18F]FES-PET assessment predicted ER expression in the biopsied metastasis with good accuracy: a sensitivity of 95% (95% CI, 89 to 97), a specificity of 80% (66 to 89), a positive predictive value (PPV) of 93% (87 to 96), and a negative predictive value (NPV) of 85% (72 to 92) in 181 of 200 evaluable patients. Quantitative [18F]FES uptake predicted ER immunohistochemistry in the corresponding metastasis with a sensitivity/specificity of 91%/69% and a PPV/NPV of 90%/71% in 156 of 200 evaluable patients. For bone metastases, PPV/NPV was 92%/81%. Meta-analysis with addition of our data has increased diagnostic performance and narrowed the 95% CIs compared with previous studies with a sensitivity/specificity of both 86% (81 to 90 and 73 to 93, respectively).In this largest prospective series so far, we established the clinical validity of [18F]FES-PET to determine tumor ER status in MBC. In view of the high diagnostic accuracy of qualitatively assessed whole-body [18F]FES-PET, this noninvasive imaging modality can be considered a valid alternative to a biopsy of a metastasis to determine ER status in newly MBC (ClinicalTrials.gov identifier: NCT01957332).
Chromatin Rewiring by Mismatch Repair Protein MSH2 Alters Cell Adhesion Pathways and Sensitivity to BET Inhibition in Gastric Cancer
Authors: Amrita M. Nargund, Chang Xu, Amit Mandoli, Atsushi Okabe, Gao Bin Chen, Kie Kyon Huang, Taotao Sheng, Xiaosai Yao, Jia Ming Nickolas Teo, Raghav Sundar, Yee Jiun Kok, Yi Xiang See, Manjie Xing, Zhimei Li, Chern Han Yong, Aparna Anand, Zul Fazreen Bin Adam Isa, Lai Fong Poon, Michelle Shu Wen Ng, Javier Yu Peng Koh, Wen Fong Ooi, Su Ting Tay, Xuewen Ong, Angie Lay Keng Tan, Duane T. Smoot, Hassan Ashktorab, Heike I. Grabsch, Melissa J. Fullwood, Bin Tean Teh, Xuezhi Bi, Atsushi Kaneda, Shang Li, Patrick Tan
Journal: Cancer Research (2022)

Abstract Mutations in the DNA mismatch repair gene MSH2 are causative of microsatellite instability (MSI) in multiple cancers. Here, we discovered that besides its well-established role in DNA repair, MSH2 exerts a novel epigenomic function in gastric cancer. Unbiased CRISPR-based mass spectrometry combined with genome-wide CRISPR functional screening revealed that in early-stage gastric cancer MSH2 genomic binding is not randomly distributed but rather is associated specifically with tumor-associated super-enhancers controlling the expression of cell adhesion genes. At these loci, MSH2 genomic binding was required for chromatin rewiring, de novo enhancer–promoter interactions, maintenance of histone acetylation levels, and regulation of cell adhesion pathway expression. The chromatin function of MSH2 was independent of its DNA repair catalytic activity but required MSH6, another DNA repair gene, and recruitment to gene loci by the SWI/SNF chromatin remodeler SMARCA4/BRG1. Loss of MSH2 in advanced gastric cancers was accompanied by deficient cell adhesion pathway expression, epithelial–mesenchymal transition, and enhanced tumorigenesis in vitro and in vivo. However, MSH2-deficient gastric cancers also displayed addiction to BAZ1B, a bromodomain-containing family member, and consequent synthetic lethality to bromodomain and extraterminal motif (BET) inhibition. Our results reveal a role for MSH2 in gastric cancer epigenomic regulation and identify BET inhibition as a potential therapy in MSH2-deficient gastric malignancies. Significance: DNA repair protein MSH2 binds and regulates cell adhesion genes by enabling enhancer–promoter interactions, and loss of MSH2 causes deficient cell adhesion and bromodomain and extraterminal motif inhibitor synthetic lethality in gastric cancer.
Single-cell sequencing: a promising approach for uncovering the mechanisms of tumor metastasis
Authors: Yingying Han, Dan Wang, Lushan Peng, Tao Huang, Xiaoyun He, Junpu Wang, Chunlin Ou
Journal: Journal of Hematology & Oncology (2022)

Abstract Single-cell sequencing (SCS) is an emerging high-throughput technology that can be used to study the genomics, transcriptomics, and epigenetics at a single cell level. SCS is widely used in the diagnosis and treatment of various diseases, including cancer. Over the years, SCS has gradually become an effective clinical tool for the exploration of tumor metastasis mechanisms and the development of treatment strategies. Currently, SCS can be used not only to analyze metastasis-related malignant biological characteristics, such as tumor heterogeneity, drug resistance, and microenvironment, but also to construct metastasis-related cell maps for predicting and monitoring the dynamics of metastasis. SCS is also used to identify therapeutic targets related to metastasis as it provides insights into the distribution of tumor cell subsets and gene expression differences between primary and metastatic tumors. Additionally, SCS techniques in combination with artificial intelligence (AI) are used in liquid biopsy to identify circulating tumor cells (CTCs), thereby providing a novel strategy for treating tumor metastasis. In this review, we summarize the potential applications of SCS in the field of tumor metastasis and discuss the prospects and limitations of SCS to provide a theoretical basis for finding therapeutic targets and mechanisms of metastasis.
Trafficking and persistence of alloantigen-specific chimeric antigen receptor regulatory T cells in Cynomolgus macaque
Authors: Gavin I. Ellis, Kimberly E. Coker, Delaine W. Winn, Mosha Z. Deng, Divanshu Shukla, Vijay Bhoj, Michael C. Milone, Wei Wang, Chengyang Liu, Ali Naji, Raimon Duran-Struuck, James L. Riley
Journal: Cell Reports Medicine (2022)

Adoptive transfer of chimeric antigen receptor regulatory T cells (CAR Tregs) is a promising way to prevent allograft loss without the morbidity associated with current therapies. Non-human primates (NHPs) are a clinically relevant model to develop transplant regimens, but manufacturing and engraftment of NHP CAR Tregs have not been demonstrated yet. Here, we describe a culture system that massively expands CAR Tregs specific for the Bw6 alloantigen. In vitro, these Tregs suppress in an antigen-specific manner without pro-inflammatory cytokine secretion or cytotoxicity. In vivo, Bw6-specific CAR Tregs preferentially traffic to and persist in bone marrow for at least 1 month. Following transplant of allogeneic Bw6
Association of Chronic Hepatitis B Infection and Antiviral Treatment With the Development of the Extrahepatic Malignancies: A Nationwide Cohort Study
Authors: Dong Hyeon Lee, Sung Won Chung, Jeong-Hoon Lee, Hwi Young Kim, Goh Eun Chung, Mi-Sook Kim, Bo Ram Yang, Joon Yeul Nam, Yun Bin Lee, Yoon Jun Kim, Jung-Hwan Yoon
Journal: Journal of Clinical Oncology (2022)

Epidemiologic studies suggest that chronic hepatitis B (CHB) is a risk factor for various primary extrahepatic malignancies. Our aim was to evaluate the associations of CHB and nucleos(t)ide analog (NA) treatment with the risk of the development of extrahepatic malignancies.We conducted an 18-month landmark analysis using nationwide claims data from the National Health Insurance Service of South Korea. Patients newly diagnosed with CHB in 2012-2014 (n = 90,944) and matched-controls (n = 685,436) were included. Patients with CHB were further classified as the NA-treated (CHB+/NA+, n = 6,539) or the NA-untreated (CHB+/NA-, n = 84,405) group. Inverse probability of treatment weighting analysis was applied to balance the treatment groups. Time-varying Cox analysis was performed to evaluate time-varying effect of NA treatment. The primary outcome was the development of any primary extrahepatic malignancy. Development of intrahepatic malignancy and death were considered as competing events.During the study period (median = 47.4 months), 30,413 patients (3.9%) developed any extrahepatic malignancy. The CHB+/NA- group had a higher overall risk of extrahepatic malignancy than the CHB+/NA+ group (adjusted subdistribution hazard ratio [aSHR] = 1.28; 95% CI, 1.12 to 1.45; P < .001) or controls (aSHR = 1.22; 95% CI, 1.18 to 1.26; P < .001). There was no difference in the risk of extrahepatic malignancy between the CHB+/NA+ group and the controls (CHB+/NA+ v control: aSHR = 0.96; 95% CI, 0.84 to 1.08; P = .48). In time-varying Cox analysis, the CHB+/NA- patients were associated with a higher risk of extrahepatic malignancy than the CHB+/NA+ patients (aSHR = 1.37; 95% CI, 1.23 to 1.52; P < .001).Patients with CHB have an elevated risk of developing primary extrahepatic malignancy. Long-term NA treatment was associated with a lower risk of extrahepatic malignancy development among patients with CHB.
Effects of Elexacaftor/Tezacaftor/Ivacaftor Therapy on Lung Clearance Index and Magnetic Resonance Imaging in Patients with Cystic Fibrosis and One or Two <i>F508del</i> Alleles
Authors: Simon Y. Graeber, Diane M. Renz, Mirjam Stahl, Sophia T. Pallenberg, Olaf Sommerburg, Lutz Naehrlich, Julian Berges, Martha Dohna, Felix C. Ringshausen, Felix Doellinger, Constanze Vitzthum, Jobst Röhmel, Christine Allomba, Susanne Hämmerling, Sandra Barth, Claudia Rückes-Nilges, Mark O. Wielpütz, Gesine Hansen, Jens Vogel-Claussen, Burkhard Tümmler, Marcus A. Mall, Anna-Maria Dittrich
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

Rationale: We recently demonstrated that triple-combination CFTR (cystic fibrosis transmembrane conductance regulator) modulator therapy with elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) improves CFTR function in airway and intestinal epithelia to 40–50% of normal in patients with cystic fibrosis (CF) with one or two F508del alleles. In previous studies, this improvement of CFTR function was shown to improve clinical outcomes; however, effects on the lung clearance index (LCI) determined by multiple-breath washout and abnormalities in lung morphology and perfusion detected by magnetic resonance imaging (MRI) have not been studied. Objectives: To examine the effect of ELX/TEZ/IVA on LCI and lung MRI scores in patients with CF and one or two F508del alleles aged ⩾12 years. Methods: This prospective, observational, multicenter, postapproval study assessed LCI and lung MRI scores before and 8–16 weeks after initiation of ELX/TEZ/IVA. Measurements and Main Results: A total of 91 patients with CF, including 45 heterozygous for F508del and a minimal function mutation (MF) and 46 homozygous for F508del, were enrolled in this study. Treatment with ELX/TEZ/IVA improved LCI in F508del/MF (−2.4; interquartile range [IQR], −3.7 to −1.1; P < 0.001) and F508del homozygous (−1.4; IQR, −2.4 to −0.4; P < 0.001) patients. Furthermore, ELX/TEZ/IVA improved the MRI global score in F508del/MF (−6.0; IQR, −11.0 to −1.3; P < 0.001) and F508del homozygous (−6.5; IQR, −11.0 to −1.3; P < 0.001) patients. Conclusions: Our data demonstrate that improvement of CFTR function by ELX/TEZ/IVA improves lung ventilation and abnormalities in lung morphology, including airway mucus plugging and wall thickening, in adolescent and adult patients with CF and one or two F508del alleles in a real-world, postapproval setting. Clinical trial registered with www.clinicaltrials.gov (NCT04732910).
Patient Navigation Increases Linkage to Care and Receipt of Direct-acting Antiviral Therapy in Patients with Hepatitis C
Authors: Joslyn Strebe, Nicole E Rich, Li Wang, Amit G Singal, Jennifer McBryde, Mauro Silva, Victoria Jackson, Hannah Fullington, Deyaun L Villarreal, Stephanie Reyes, Bertha Flores, Mamta K Jain
Journal: Clinical Gastroenterology and Hepatology (2022)

Patient navigation interventions can improve health outcomes in underserved, low-income, and racial and ethnic minority groups, who often experience health disparities. We examined the effectiveness of patient navigation to improve linkage to hepatitis C virus (HCV) treatment receipt in a socioeconomically disadvantaged, racially diverse patient population.We performed a pre-post analysis evaluating the effectiveness of a patient navigation program among baby boomers who tested positive for HCV in a safety-net health system. The usual care group (June 2013 to May 2015) and patient navigation group (January 2016 to December 2017) were balanced using a stabilized inverse probability of treatment weighting approach. We used logistic regression analyses to evaluate associations between patient navigation and linkage to care for HCV treatment evaluation, treatment initiation, and sustained virologic response.Among 1353 patients (62% black, 61% uninsured, 16% homeless), 769 were in the usual care group, and 584 were in the patient navigation group. The patient navigation group had significantly higher odds of linkage to care (odds ratio [OR], 3.7; 95% confidence interval [CI], 2.9-4.8) and treatment initiation (OR, 3.2; 95% CI, 2.3-4.2) within 6 months. The patient navigation group continued to have increased linkage to care (OR, 3.4; 95% CI, 2.7-4.3) and treatment initiation (OR 2.3; 95% CI, 1.7-3.0) at 12 months. However, there was no significant difference in sustained virologic response between the groups (86.9% vs 86.1%; P = .78).Patient navigation was associated with significantly increased linkage to care and treatment initiation among patients with HCV infection. Patient navigation programs can be used to promote HCV elimination among traditionally difficult-to-reach patient populations.
Idelalisib activates AKT via increased recruitment of PI3Kδ/PI3Kβ to BCR signalosome while reducing PDK1 in post-therapy CLL cells
Authors: Murali K. Mamidi, Hasan Mahmud, Guru P. Maiti, Mariana T. Mendez, Stacey M. Fernandes, Sara K. Vesely, Jennifer Holter-Chakrabarty, Jennifer R. Brown, Asish K. Ghosh
Journal: Leukemia (2022)
Arid Airways: Airway Mucosal Injury with Nonhumidified Invasive Ventilation
Authors: Norman M. Lee, Christine M. Bojanowski, Ramsy A. Abdelghani
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

"Arid Airways: Airway Mucosal Injury with Nonhumidified Invasive Ventilation." American Journal of Respiratory and Critical Care Medicine, 206(2), pp. 217–218
Treatment With Etirinotecan Pegol for Patients With Metastatic Breast Cancer and Brain Metastases
Authors: Debu Tripathy, Sara M. Tolaney, Andrew D. Seidman, Carey K. Anders, Nuhad Ibrahim, Hope S. Rugo, Chris Twelves, Véronique Diéras, Volkmar Müller, Yining Du, Sue L. Currie, Ute Hoch, Mary Tagliaferri, Alison L. Hannah, Javier Cortés, Daphne Tsoi, Susan Chua, Elgene Lim, Craig R. Underhill, Philip R. Clingan, Arlene Chan, Ines Deleu, Marleen Borms, Francois P. Duhoux, Ahmad Awada, Marie-Pascale Graas, Jean-Luc Canon, Konstantinos Papadimitriou, Thierry Velu, Maureen Trudeau, Michael Thirlwell, Philippe Barthelemy, Miruna Timar David, Delphine Loirat, Mireille Mousseau, Hugues Bourgeois, Jean-Christophe Thery, Tanja Fehm, Pauline Wimberger, Margarita Tokar, Georgeta Fried, Ido Wolf, Luca Gianni, Marco Colleoni, Michelino De Laurentiis, Francesco Cognetti, Michele Orditura, Carmelo Bengala, Cláudia Vieira, Rita Teixeira de Sousa, Maria de Fatima Cabral da Rocha Cardoso, Josefina Cruz Jurado, Jose Angel Garcia-Saenz, Patricia Gomez, Manuel Ruiz-Borrego, Luis De La Cruz-Merino, José Manuel Perez Garcia, Pedro Sánchez-Rovira, Vanesa Ortega, Maria Fernández Abad, Srinivasan Madhusudan, Anne Armstrong, Pavani Chalasani, Lee Schwartzberg, Simon Khagi, David Potter, Alejandra Perez, Nicole Williams, Michelle Melisko, Eric Harris, Foluso Ademuyiwa, Jennifer Specht, DiSean Kendall, Robyn Young, Petros Nikolinakos, Katherine H.R. Tkaczuk
Journal: JAMA Oncology (2022)

Patients with breast cancer and brain metastases (BM) have a poor prognosis and high clinical need for novel treatments; however, historically, studies have often excluded these patients. Although the BEACON study did not meet its primary end point, treatment with etirinotecan pegol vs chemotherapy of the physician's choice for patients with advanced breast cancer demonstrated a significant improvement in overall survival (OS) for the prespecified patient subgroup with preexisting, pretreated, and nonprogressive BM.
Cardiovascular Outcomes in Collegiate Athletes After SARS-CoV-2 Infection: 1-Year Follow-Up From the Outcomes Registry for Cardiac Conditions in Athletes
Authors: Bradley J. Petek, Nathaniel Moulson, Jonathan A. Drezner, Kimberly G. Harmon, Stephanie A. Kliethermes, Timothy W. Churchill, Manesh R. Patel, Aaron L. Baggish, Irfan M. Asif, Aaron L. Baggish, James Borchers, Jonathan A. Drezner, Katherine M. Edenfield, Michael S. Emery, Kyle Goerl, Brian Hainline, Kimberly G. Harmon, Pei-Ni Jone, Jonathan H. Kim, Stephanie Kliethermes, William E. Kraus, Rachel Lampert, Matthew Leiszler, Benjamin D. Levine, Matthew W. Martinez, Nathaniel Moulson, Francis G. O’Connor, Manesh R. Patel, Bradley J. Petek, Dermot Phelan, Lawrence D. Rink, Herman A. Taylor, Carl Ade, Aryan Aiyer, Jarrah Alfadhli, Chloe Amaradio, Scott Anderson, Stephanie Arlis-Mayor, Jonathan S. Aubry, Andrea Austin, Brenden J. Balcik, Timothy Beaver, Nicolas Benitez, Brant Berkstresser, Thomas M. Best, Tiffany Bohon, Jonathan P. Bonnet, Elizabeth Boyington, James Bray, Jenna Bryant, Jeffrey Bytomski, Sean Carnahan, Rachel Chamberlain, Samantha Charters, Nicholas Chill, Daniel E. Clark, Douglas Comeau, Laura E. Cook, Deanna Corey, Amy Costa, Marshall Crowther, Tarun Dalia, Craig Davidson, Kaitlin Davitt, Annabelle De St. Maurice, Peter N. Dean, Jeffrey M. Dendy, Katelyn DeZenzo, Courtney Dimitris, Jeanne Doperak, Calvin Duffaut, Craig Fafara, Katherine Fahy, Jason Ferderber, Megan Finn, Frank A. Fish, R. Warne Fitch, Angelo Galante, Todd Gerlt, Amy Gest, Carla Gilson, Jeffrey Goldberger, Joshua Goldman, Erich Groezinger, Jonathan R. Guin, Heather Halseth, Joshua Hare, Beth Harness, Nicolas Hatamiya, Julie Haylett, Neal Hazen, Sean G. Hughes, Yeun Hiroi, Amy Hockenbrock, Amanda Honsvall, Jennifer Hopp, Julia Howard, Samantha Huba, Mustafa Husaini, Lindsay Huston, Calvin Hwang, Laura Irvin, Val Gene Iven, Robert Jones, Donald Joyce, Kristine Karlson, Jeremy Kent, Christian F. Klein, Chris Klenck, Michele Kirk, Jordan Knight, Laura Knippa, Madeleine Knutson, Louis E. Kovacs, Yumi Kuscher, Andrea Kussman, Chrissy Landreth, Amy Leu, Dylan Lothian, Maureen Lowery, Andrew Lukjanczuk, John M. MacKnight, Lawrence M. Magee, Marja-Liisa Magnuson, Aaron V. Mares, Anne Marquez, Grant McKinley, Scott Meester, Megan Meier, Pranav Mellacheruvu, Christopher Miles, Emily Miller, Hannah Miller, Raul Mitrani, Aaron J. Monseau, Benjamin Moorehead, Robert J. Myerburg, Greg Mytyk, Andrew Narver, Aurelia Nattiv, Laika Nur, Brooke E. Organ, Meredith Pendergast, Frank A. Pettrone, Jordan Pierce, Sourav K. Poddar, Diana Priestman, Ian Quinn, Fred Reifsteck, Morgan Restivo, James B. Robinson, Ryan Roe, Thomas Rosamond, Carrie Rubertino Shearer, Diego Riveros, Miguel Rueda, Takamasa Sakamoto, Brock Schnebel, Ankit B. Shah, Alan Shahtaji, Kevin Shannon, Polly Sheridan-Young, Jonathon H. Soslow, Siobhan M. Statuta, Mark Stovak, Andrei Tarsici, Kenneth S. Taylor, Kim Terrell, Matt Thomason, Jason Tso, Daniel Vigil, Francis Wang, Jennifer Winningham, Susanna T. Zorn
Journal: Circulation (2022)
Quantitative Luminescence Photography of a Swellable Hydrogel Dressing with a Traffic‐Light Response to Oxygen (Adv. Healthcare Mater. 10/2022)
Authors: Haley L. Marks, Katherine Cook, Emmanuel Roussakis, Juan Pedro Cascales, Jeremy T. Korunes‐Miller, Mark W. Grinstaff, Conor L. Evans
Journal: Advanced Healthcare Materials (2022)

Luminescence Oxygen & pH Sensing A swellable color-changing hydrogel dressing featuring a red-to-green “traffic light” response to oxygen is developed in article number 2101605 by Conor L. Evans and co-workers. Using simple macroscopic photography, intensity-independent quantification of oxygen is enabled though image conversion to the HSB color space, while the green channel intensity can be used to monitor pH. The “traffic light” response is maintained despite high autofluorescence from skin, thereby providing clinician-friendly naked-eye feedback. Cover art courtesy of Juan Pedro Cascales Sandoval.
Abstract A034: Bayesian adaptive design for phase I drug combination trials
Authors: Ying Yuan, Suyu Liu
Journal: Cancer Research (2022)

Abstract Drug combination therapy is the most commonly used approach to overcome acquired resistance to cancer therapy. Designing phase I drug combination trials faces several challenges beyond the conventional single-agent dose escalation studies, e.g., two-dimensional dose space and partial order in toxicity. In this presentation, we will overview novel Bayesian adaptive designs for drug combination trials. In particularly, we will focus on model-assisted designs that are simply to implement, while yielding superior operating characteristics. Trial example and software will be provided to illustrate the application of the novel designs. Citation Format: Ying Yuan, Suyu Liu. Bayesian adaptive design for phase I drug combination trials [abstract]. In: Proceedings of the AACR Special Conference on the Evolutionary Dynamics in Carcinogenesis and Response to Therapy; 2022 Mar 14-17. Philadelphia (PA): AACR; Cancer Res 2022;82(10 Suppl):Abstract nr A034.
Race, Overdose Deaths, and Years of Lost Life—Reply
Authors: O. Trent Hall, Candice Trimble, Stephanie Garcia
Journal: JAMA Pediatrics (2022)

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